POS1576 AN UNUSUAL INITIAL PRESENTATION OF VEXAS SYNDROME
Authors: A. S. Galindo-Feria, K. Chatzidionysiou
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset multisystem autoinflammatory disease caused by a somatic mutation in the ubiquitin-activating enzyme (UBA1) gene in myeloid or erythroid precursor cells, causing a variety of symptoms including fever, cytopenia, vacuoles in myeloid and erythroid progenitors, dysplastic bone marrow, neutrophilic dermatosis, pulmonary infiltrates, chondritis and/or vasculitis. <h3>Objectives</h3> This report describes an atypical initial presentation of peri-orbital inflammation and neurological manifestations associated with this newly recognized syndrome. <h3>Methods</h3> This is a case report. <h3>Results</h3> An 82-year-old male with insulin-treated diabetes mellitus type II, prostate hyperplasia and chronic atrial fibrillation, presented with persistent unilateral peri-orbital swelling and pain for 6 months. An initial evaluation in the ophthalmology department with biopsy showed no evidence of malignancy, myositis, vasculitis or IgG4-related disease. Due to significantly elevated inflammatory markers (CRP 250-300 mg/L, ESR around 100 mm/h), the patient received high-dose glucocorticoids (60mg Prednisolone) with a good clinical response. During the tapering of Prednisolone, the patient developed a maculopapular skin rash in the lower extremities. Skin biopsy showed signs of urticaria-like dermatitis, while immunofluorescence examination was negative. In the following months, he was hospitalized three times due to recurrent fever, generalized weakness, fatigue and general asthenia. Extensive evaluation regarding infectious and neoplastic causes was negative. An extensive autoimmune panel (including ANA and ANCA) was tested and came out negative. CT scan of the thorax and abdomen was unremarkable. During the last hospitalization, he developed expressive aphasia and fascial paresis. MRI of the brain showed signs of leptomeningeal enhancement. Examination of the cerebral fluid showed pleocytosis (leucocyte count 124, with monocytosis), while all cultures were negative. He came to the rheumatology department in November 2022 for further evaluation. He had generalized myalgias and arthralgias but no arthritis. The skin rash had disappeared. The inflammatory markers were still highly elevated and he had a mild anemia, normocytic and normochromic, but no thrombocytopenia or leukopenia. PET-CT scan showed hyperactive bone marrow, while subsequent biopsy showed normal hematopoiesis without signs of dysplasia and no vacuoles. Endoscopic evaluations revealed no pathological findings. Prednisolone was re-introduced after PET-CT with good regress of the symptoms. Repeated MRI of the brain showed regression of the area with enhancement while all neurological symptoms had subsided. A few weeks later, we received the result of the genetic testing showing a mutation of the UBA1 gene, confirming the diagnosis of VEXAS. Our patient had already started methotrexate as a cortisone-sparing agent and started tapering off Prednisolone, so far with reasonable clinical response. <h3>Conclusion</h3> VEXAS syndrome should be suspected in elderly patients (especially males) with systemic inflammation when other common conditions are excluded. Orbital/peri-orbital inflammation and neurological manifestations can occur and should raise the suspicion of VEXAS. <h3>References</h3> [1]Beck D.B. Ferrada M.A. Sikora K.A. et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med. 2020; 383: 2628-2638 [2]Holmes A, Thant A, Correy R, Vilain R. Inflammatory pseudotumour arising secondary to VEXAS syndrome. Pathology. 2023 Feb;55(1):161-163. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Angeles Shunashy Galindo-Feria: None declared, Katerina Chatzidionysiou Grant/research support from: Galapagos.